Real-World Outcomes of Non-Transfusion-Dependent Patients with MDS Treated with Luspatercept

A roundtable discussion, moderated by Hana Safah, MD, of the Tulane University School of Medicine, focused on the latest data in myelodysplastic syndromes presented at the 65th ASH Annual Meeting & Exposition. Dr. Safah was joined by Jamile Shammo, MD; Andrew Brunner, MD; and Tiffany Tanaka, MD.

In the next segment of the roundtable series, the panel discusses whether starting treatment with luspatercept sooner in patients with MDS is beneficial.

Watch the next segment in this series.

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Dr. Safah: If you also can share with us the real-world retrospective study of non-transfusion-dependent patients with myelodysplastic syndromes (MDS) treated with luspatercept. It’s a health care claim database study, and they looked at the data or the results or what happened to patients who somehow, and I wonder how, they received luspatercept before they became transfusion-dependent. Can you share that with us?

Dr. Shammo: I think that the real-world data evidence can be very helpful at times because you may derive hints as to the responses or perhaps even physician’s preferences and patients that may not have been included in the clinical trials. I think in that sense, there’s some benefit to understanding real-world data. In this particular analysis, there was essentially an evaluation of over 800 patients, most of whom I would say, at least two-thirds, were non-transfusion-dependent, to tackle the question, what happens if you actually treated such patients with treatments prior to them becoming transfusion-dependent? All of us would like to have an answer to this question because essentially all MDS patients will ultimately become transfusion-dependent.

Why wait and would starting the drug sooner be more beneficial? In this analysis at least, and we all know all the issues that may come with the real-world data analysis, but it appears that patients who are receiving luspatercept maintain other treatment immunity, if you will. They responded and they remained on this drug without needing additional treatment. The hope is that preventing or I should say starting the drug sooner in patients who may not be transfusion-dependent may actually delay transfusion dependency. I wonder what my colleagues feel, but I feel like this should be a challenge and perhaps reanalyzed the frontline setting.

Dr. Safah: Thank you. I think there are trials now going on with the spider luspatercept, Dr. Brunner.

Dr. Brunner: I was going to say, I think it’s a real challenge for us to try to tell the future: Would this patient have gone a year without needing a transfusion anyway? Or is intervening somehow changing the course of that? I think the data that we have from MDS in general that gives us some insight into that possibility is maybe the SINTRA-REV data showing early intervention with low-dose lenalidomide for two years can delay the time to transfusion-independence. But even with that data, I myself struggle with what’s the best course of action for a patient. I think that my view of a lot of this data is that intervening early, not waiting until people become heavily transfusion-dependent, not letting them start to mount the complications of red cell needs.

If you intervene early with growth factor, if you intervene early with luspatercept, they’re more likely to work, they’re more likely to get better responses, and those responses can be robust. I guess I view that kind of real-world data as maybe not going to change my practice of now treating everybody who’s transfusion-independent, but not letting people become heavily transfusion-dependent. Once they start to have transfusion, that should be a signal in my head that we need to initiate some sort of treatment change. I guess I integrate the data in my practice that way, that we have tools and we should be using them early in disease.

Dr. Shammo: Yes. Sometimes what happens is that you see this patient who may have a hemoglobin of let’s say 11, and then two or three months later they’re 10.5 and then two months later they’re 10 or 9.5. They’re not transfusion-dependent, but they are anemic, they are fatigued. Data like this may actually help in this particular patient.

Dr. Safah: Perfect. I think as I said, there is a trial with luspatercept looking at patients who are not transfusion-dependent yet comparing to placebo, and then we will be awaiting the results of the ELEMENT trial.